Scutellarin is the main effective constituent of breviscapine, a flavonoid mixture isolated from the dried whole plant of Erigeron breviscapus (Vant.) Hand-Mazz, and valsartan is used as an antihypertensive drug. These two drugs have already been clinically used together to treat diabetic nephropathy (DN) in China, and the combined medications showed some enhanced protection against DN. The aim of this study is to investigate the potential pharmacokinetic interaction between scutellarin and valsartan in rats. Breviscapine injection (20 mg x kg(-1), i.v.) and valsartan (15 mg x kg-, i.g.), either alone or together were given to 18 male Sprague-Dawley rats. Concentrations of scutellarin and valsartan were quantified by HPLC, and pharmacokinetic parameters were calculated by non-compartmental methods. We found that the pharmacokinetic parameters of scutellarin altered significantly after co-administration of oral valsartan. The plasma clearance (CL(p)) and the bile clearance (CL(b)) of scutellarin were reduced significantly in the presence of valsartan. After oral administration of valsartan with or without intravenous scutellarin, however, the pharmacokinetic parameters of valsartan were comparable. In conclusion, our data suggests that the concurrent use of valsartan reduces the biliary excretion of scutellarin, and this may be due to the inhibitory effect of valsartan on the biliary excretion of scutellarin mediated by Mrp2 (Multidrug resistance-associated protein 2).

Pancreatic adenocarcinoma up-regulated factor(PAUF),a newly discovered gene,is highly expressed in pancreatic cancer.PAUF promotes the metastasis and progression of pancreatic cancer through many ways,such as the activation of signal pathway (CXCR4,β-catenin,TPL2/MEK/ERK,FAK/Scr),increasing the adhesiveness of pancreatic cancer cells,promoting angiogenesis and vascular permeability.Simultaneously,CXCR4,β-catenin,TPL2/MEK/ERK and FAK/Scr are closely related with gemcitabine-resistance.Based on this theory,we infer that PAUF plays a role in gemcitabine-resistance of pancreatic cancer cells.So far,no related research has been done domestic and overseas.The research may find a clue for the mechanism of chemotherapy-resistance and provide a new target spot for the therapy of pancreatic cancer.

Objective:To study the clinical application of laparoscopic combined with multi-video debridement in treatment of complicated infectious pancreatic necrosis (CIPN).Methods:The clinical data of 34 patients with CIPN who were treated at the Department of General Surgery, Xuanwu Hospital, Capital Medical University from August 2017 to December 2019 were retrospectively studied. Based on the different video methods used, these patients were divided into 3 groups: the laparoscopic combined with intraoperative ultrasound group, the laparoscopic combined with choledochoscopy group and the laparoscopic group. The number of operations, operation time, blood loss, postoperative complication rates, mortality rates and total length of hospital stay were compared.Results:There were 13 patients in the laparoscopic combined with intraoperative ultrasound group, with age of (56.4±13.4) years. There were 7 patients in the laparoscopic combined with choledochoscopy group, with age of (48.0±8.4) years. There were 14 patients in the laparoscopic group with age of (51.4±15.6) years. The number of operations of the laparoscopic combined with intraoperative ultrasound group, the laparoscopic combined with choledochoscopy group and the laparoscopic group were (2.2±1.1), (1.6±0.8), (2.9±1.4), respectively. The number of operations of the laparoscopic combined with choledochoscopy group were significantly less than that of the laparoscopic group ( P<0.05), but there were no significant differences among the other groups ( P>0.05). The operation time of the laparoscopic combined with intraoperative ultrasound group, the laparoscopic combined with choledochoscopy group and the laparoscopic group were (70.5±22.9) min, (65.7±19.9) min, (51.5±15.4) min, respectively. The operation time of the laparoscopic combined with intraoperative ultrasound group was significantly longer than that of the laparoscopic group ( P<0.05), but there were no significant differences among the other groups ( P>0.05). There were no differences in blood loss, postoperative complication rate, mortality rates and total lengths of hospital stay among the three groups ( P>0.05). Conclusion:Laparoscopic combined with multi-video debridement after making full use of the advantages of each of the video methods, can be used to improve treatment outcomes of patients with CIPN.

Metabolic profile of bile acids was used to evaluate hepatotoxicity of mice caused by ethanol extraction of Dioscorea bulbifera L. (ethanol extraction, ET) and diosbulbin B (DB), separately. Ultra-performance liquid chromatography coupled with quadrupole mass spectrometry (UPLC-MS) was applied to determine the contents of all kinds of endogenous bile acids including free bile acids, taurine conjugates and glycine conjugates. Obvious liver injuries could be observed in mice after administrated with ET and DB. Based on the analysis using principle components analysis (PCA), toxic groups could be distinguished from their control groups, which suggested that the variance of the contents of bile acids could evaluate hepatotoxicity caused by ET and DB. Meanwhile, ET and DB toxic groups were classified in the same trends comparing to control groups in the loading plot, and difference between the two toxic groups could also be observed. DB proved to be one of the toxic components in Dioscorea bulbifera L. Bile acids of tauroursodeoxycholic acid (TUDCA), taurochenodeoxycholic acid (TCDCA), taurocholic acid (TCA), taurodeoxycholic acid (TDCA), cholic acid (CA) and others proved to be important corresponds to ET and DB induced liver injury according to analysis of partial least square-discriminant analysis (PLS-DA) and the statistical analysis showed that there were significant differences between the control groups and toxic groups (P < 0.01). Furthermore, good correlation could be revealed between the foregoing bile acids and ALT, AST. It indicated that taurine conjugated bile acids as TUDCA, TCDCA, TCA and TDCA along with CA could be considered as sensitive biomarkers of ET and DB induced liver injury. This work can provide the base for the further research on the evaluation and mechanism of hepatotoxicity caused by Dioscorea bulbifera L.

Objective To observe the influence on the sensitivity of pancreatic cancer cell line BxPC-3 to gemcitabine of silencing PAUF gene.Methods BxPC-3 cells,which overexpress PAUF,was stably transfected with PAUF-shCtrl and PAUF-shRNA to establish BxPC-3_shCtrl and BxPC-3_shPAUF cells as control and experiment group.Then the mRNA and protein expression level of PAUF in these two cell lines were detected by RT-PCR and western blot,respectively.The growth inhibition rates of these two cell lines treated with different concentrations of gemcitabine (0,3.1,6.25,12.5,25,50,100,200 nmol/L) were detected by MTT.Apoptosis rates in the cells treated with different concentrations of gemcitabine (0,75,100 nmol/L) were then observed by flow cytometry.Results The relative PAUF mRNA expression level in BxPC-3_shCtrl and BxPC-3 cells were 1.00 ± 0.06 and 0.83 ± 0.07,which were significantly high er than that in BxPC-3_shPAUF cells (0.25 ± 0.02;both P ＜ 0.05).The relative PAUF protein expression level in BxPC-3_shCtrl and BxPC-3 cells were 0.89 ± 0.07 and 0.95 ± 0.04,which were significantly high er than that in BxPC-3_shPAUF cells (0.31 ± 0.03;both P ＜ 0.05).The IC50 value of gemcitabine to BxPC-3_shCtrl cell was (22.88 ± 2.43) nmol/L,which was significantly higher than that of BxPC-3_shPAUF cells [(1.06 ± 0.02) nmol/L;P ＜ 0.05];apoptosis rate of BxPC-3_shPAUF cells treated by gemcitabine increased faster than that of BxPC-3_shCtrl cells.Conclusion PAUF silencing could greatly enhance the sensitivity of BxPC-3 cells to gemcitabine.

The application of minimally invasive technique in infected pancreatic necrosis has been matured gradually but has controversy and challenges in the same time. This paper further discusses the advantages, timing, combination of multi-video-assisted debridement and post-operative management of minimally invasive surgery. The greatest advantage of minimally invasive surgery lies in "No intervention for normal abdominal space" which not only can reduce unnecessary injury and complication but also promote intestinal function recovery after operation. The principle of delayed operation is controversial. Early PCD and "one-step" minimally invasive laparoscopic debridement and drainage have both achieved good results. The combination of multi-video-assisted minimally invasive technique can make up for the shortage of single technique to shorten the operation time and improve the debridement efficiency of patients with complicated infected pancreatic necrosis and provide new ideas for video-assisted debridement. Fully debridement and drainage are the key points and standardization for post-operative management. It′s a difficult problem and an important research direction to apply minimally invasive technique for patients with infected pancreatic necrosis reasonably and scientifically.

Objective To investigate of the MMI-166 on the expression of MMP-2,MMP-9 and the cell apoptosis of nude mouse xenografts of SW1990 human pancreatic cancer cells.Methods Establishment of control and experimental groups,randomly,the human pancreatic cancer xenograft model of SW1990 was constructed.The control group was treated with normal saline,and experimental group was treated with MML-166 (200 mg · kg-1 · d-1).The tumor volume and tumor inhibition rate was measured by vernier caliper through length and short diameter.The expression of MMP-2 and MMP-9 protein was observed using immunohistochemistry in the tumor tissues.Apoptosis index was detected by deoxynucleotidyl transferase-mediated nick end labeling (TUNEL method).Results The tumor volume of MMI-166 group (1252.30± 464.84) mm3 was less than the control group (2241.82±208.06) mm3,significantly.The inhibition rate was 34.47％ between the experimental groups (treat with MMI-166) (1.42±0.15) g and control group (2.17±0.20) g.The expression of MMP-2 (2.80 ± 1.10) ％ and MMP-9 (2.60 ± 1.52) ％ protein was significantly downregulated in MMI-166 group,compared with the control group.Apoptotic index in the experimental group (75.60±9.71) ％ was higher than the control group (17.40 ± 10.14) ％,significantly.Conclusion The mechanism of MMI-166 inhibiting pancreatic tumor growth and inducing apoptosis may be related to the suppression of MMP-2 and MMP-9 protein expression.

Lavage has been used in the treatment of infected pancreatic necrosis(IPN) for a long time.It can be divided into peritoneal lavage and necrotic cavity lavage according to different parts of lavage.At present,peritoneal lavage is rarely used,while necrotic cavity lavage is widely used in laparotomy,minimally invasive surgery and endoscopic debridement and drainage for IPN patients.However,there is no unified standard for the type,method,duration and indication of stopping lavage.The application of lavage is controversial: proponents think that necrotic cavity lavage can dilute and remove residual or new necrotic tissue,remove inflammatory mediators and reduce the times of debridement,etc.While opponents think that lavage can not significantly reduce the concentration of phospholipase A2 and other bioactive substances,and is easy to form abscess and peripancreatic sepsis and cause infection to spread into the abdominal cavity and form peritonitis.In conclusion,necrotic cavity lavage can benefit some patients,especially those with smaller drainage diameter who underwent endoscopic debridement and percutaneous catheter drainage.However,whether it is necessary for patients with larger drainage diameter who underwent laparotomy or video-assisted debridement still needs to be further studied by randomized controlled trials.

The application of minimally invasive technique in infected pancreatic necrosis has been matured gradually but has controversy and challenges in the same time. This paper further discusses the advantages, timing, combination of multi?video?assisted debridement and post?operative management of minimally invasive surgery. The greatest advantage of minimally invasive surgery lies in"No intervention for normal abdominal space"which not only can reduce unnecessary injury and complication but also promote intestinal function recovery after operation. The principle of delayed operation is controversial. Early PCD and"one?step"minimally invasive laparoscopic debridement and drainage have both achieved good results. The combination of multi?video?assisted minimally invasive technique can make up for the shortage of single technique to shorten the operation time and improve the debridement efficiency of patients with complicated infected pancreatic necrosis and provide new ideas for video?assisted debridement. Fully debridement and drainage are the key points and standardization for post?operative management. It′s a difficult problem and an important research direction to apply minimally invasive technique for patients with infected pancreatic necrosis reasonably and scientifically.

Lavage has been used in the treatment of infected pancreatic necrosis(IPN) for a long time.It can be divided into peritoneal lavage and necrotic cavity lavage according to different parts of lavage.At present,peritoneal lavage is rarely used,while necrotic cavity lavage is widely used in laparotomy,minimally invasive surgery and endoscopic debridement and drainage for IPN patients.However,there is no unified standard for the type,method,duration and indication of stopping lavage.The application of lavage is controversial: proponents think that necrotic cavity lavage can dilute and remove residual or new necrotic tissue,remove inflammatory mediators and reduce the times of debridement,etc.While opponents think that lavage can not significantly reduce the concentration of phospholipase A2 and other bioactive substances,and is easy to form abscess and peripancreatic sepsis and cause infection to spread into the abdominal cavity and form peritonitis.In conclusion,necrotic cavity lavage can benefit some patients,especially those with smaller drainage diameter who underwent endoscopic debridement and percutaneous catheter drainage.However,whether it is necessary for patients with larger drainage diameter who underwent laparotomy or video-assisted debridement still needs to be further studied by randomized controlled trials.